Project Summary/Abstract Proteopathies are a class of at least 71 diseases characterized by the accumulation of protein aggregates. Protein aggregates are caused by an imbalance in protein homeostasis resulting in the accumulation of misfolded proteins. One major question in biomedical research is: How do cells recognize and deal with misfolded proteins? Serendipitously, we found that the model organism Dictyostelium discoideum normally expresses proteins with long polyglutamine tracts that cause one class of proteopathy. We have recently shown that Dictyostelium have an extraordinary ability to resist aggregation of a polyglutamine expanded protein know to aggregate in other model organisms. Here we propose to investigate mechanisms utilized by Dictyostelium to resist polyglutamine aggregation and explore novel aspects of the Dictyostelium protein quality control network.